Summary: Uganda is the only country in Africa where both forms of the Human African Trypanosomiasis (HAT) disease exist; chronic gambiense disease in the northwest and acute rhodesiense disease in the southeast. Recent expansions of HAT from the traditional foci in the southeast to new territories in central Uganda, which previously were disease-free, have recently been reported. Possible merger of the two disease belts in central Uganda would create a major public health crisis given the differences in diagnostics and treatment associated with the two forms of disease. This FIRCA will investigate the factors contributing to the recent expansion of disease foci in central Uganda so that effective control methods can be implemented. The proposed studies build on the findings of the Parent Grant (NIAID R01Al068932), which addresses the molecular ecology and evolutionary genetics aspect of Glossina f. fuscipes (Gff) in the rhodesiense and gambiense foci in Uganda, respectively. Parent grant results have shown that tsetse populations in the gambiense foci in the northwest are genetically highly differentiated from the rhodesiense foci in the SE. Here we will investigate whether Gff flies expanding from southeast areas, where historical HAT foci exist, transmit rhodesiense disease now emerging in central Uganda. In addition, we will investigate whether the presence of a second vector species, Glossina pallidipes, may be fueling the maintenance of rhodesiense epidemics by enhancing the animal reservoirs of HAT. Results from this investigation will immediately be relevant for the ongoing vector control program in Uganda. This proposal will also result in significant capacity building both in theory and experimental methods on HAT epidemiology at National Livestock Resources Institute in Tororo Uganda, where the majority of the work will be performed.